Transition metal (II) complexes of hydrazones derived from tetralone: synthesis, spectral characterization, in vitro antimicrobial and cytotoxic studies

Research on Chemical Intermediates

https://doi.org/10.1007/s11164-021-04413-x

Transition metal (II) complexes of hydrazones derived

from tetralone: synthesis, spectral characterization, in vitro

antimicrobial and cytotoxic studies

J. Devi¹· S. Sharma^1,2· S. Kumar¹· D. K. Jindal³· P. P. Dutta^4,6· D. Kumar⁵

Received: 14 November 2020 / Accepted: 30 January 2021

Abstract

A series of transition metal (II) complexes with general formula [M(L¹⁻⁴)₂(H₂O)₂]

(where M=Co(II), Ni(II), Cu(II) and Zn(II)) was synthesized by the reaction of

metal(II) acetates with hydrazones [HL¹–HL⁴] obtained from condensation of

tetralone with hydrazide derivatives. The characterization of synthesized compounds

(1–20) was done by using elemental analysis, diferent spectral studies (UV–Vis,

¹H NMR, ¹³C NMR, FT-IR, mass, ESR and fuorescence), magnetic susceptibility,

* J. Devi

jaya.gju@gmail.com

S. Sharma

somsamainia@gmail.com

S. Kumar

sanjeevbagri2221@gmail.com

D. K. Jindal

deepakjindal44@yahoo.com

P. P. Dutta

partha184@gmail.com

D. Kumar

guptadeepak002@gmail.com

1

Department of Chemistry, Guru Jambheshwar University of Science and Technology,

Hisar 125001, India

2

Department of Chemistry, Government College Hisar, Hisar 125001, India

3

Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science

and Technology, Hisar 125001, India

4

Institute of Advanced Studies in Science & Technology, Life Science Division,

Guwahati 781035, Assam, India

5

School of Pharmaceutical Sciences, Shoolini University, Solan 173212, Himachal Pradesh,

India

6

Faculty of Pharmaceutical Science, Assam Down Town University, Panni khaiti,

Guwahati 781026, Assam, India

Vol.:(0123456789)

1 3

J. Devi et al.

molar conductance measurement and thermal (DTA, TGA and DTG) analysis. The

characterization results suggested the bidentate nature of the hydrazones, which

chelate with the metal ion via nitrogen of (C=N) group and deprotonated carbonyl

oxygen in the enolized form, resulting in stable, non-volatile octahedral complexes.

The antimicrobial potential of the compounds was evaluated against four bacterial,

i.e. (S. aureus, B. subtilis, P. aeruginosa and E. coli), and two fungal species, i.e.

(A. niger and C. albicans), by a serial dilution method with complexes 15 and 16 as

most active compounds against microbes. All the compounds were also tested for its

cytotoxicity (in vitro) against three human cancer cell lines (A549, HeLa and MCF-

7) and one normal cell line (L₆) by the MTT assay, which focussed on an increased

activity of compounds 7 and 15 towards A549, MCF-7 and HeLa cancer cell line

with IC₅₀values ranging from 10.76 to 16.42 μg/mL, and compounds were found

to be non-toxic towards L₆cell line as compared to the standard drug doxorubicin.

The results demonstrated that complexation enhanced the biological activity of

compounds.

Graphic abstract

The synthesized compounds (1–20) were screened for antitumor activities against

A549, MCF7, Hela cancer cell lines. Copper complex (7) and (15) was found to be

the most active antitumor agent and less toxic against L6—Rat myoblast normal cell

line than standard doxorubicin.

Keywords Hydrazone · Bidentate · Octahedral · Antimicrobial · Anticancer

1 3

Transition metal (II) complexes of hydrazones derived from…

Abbreviations

DME

M Dulbecco’s modifed Eagle’s medium

DMF

Dimethylformamide

DMSO

Dimethyl sulfoxide

DMSO-d6 Deuterated dimethyl sulfoxide

ESR

TGA

DTA

MS

Electron spin resonance

Thermal gravimetric analysis

Diferential thermal analysis

Mass spectra

FAB

FT-IR

A549

HeLa

MCF7

L₆

Fast atom bombardment

Fourier transform infrared spectroscopy

Human lung carcinoma cell line

Human cervical carcinoma cell line

Human breast carcinoma cell line

Rat myoblast cell line normal

MTT

NMR

IC₅₀

3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide

Nuclear magnetic resonance

Concentration of drug required to inhibit the growth of 50% of tumour

cells

Introduction

Cancer or malignant neoplasm is one of the most widespread and highly feared

diseases for human life causing death nowadays in both developing and devel-

oped countries. Cancer results from the uncontrolled multiplication of ingenious

modifed normal human cells. Researchers throughout the globe have contributed

signifcantly towards the anticancer drug development research. Cisplatin (cis-

diamminedichloroplatinum(II)), a platinum metal-based drug, was a major develop-

ment in cancer treatment [1], but its adverse efects such as sickness, kidney and

liver failure, heavy metal toxicity and drug resistance [2] promoted researchers

to discover new metallodrugs that are less toxic, economic, target specifc with a

higher efciency.

In the last few decades, the applications of transition metal complexes for the

medical therapy of cancer are extensively investigated, and consequently, they were

acknowledged as promising anticancer agents. Transition metal complexes demon-

strated various therapeutic properties and are widely used in medicine as well as

have other applications also [3]. The ligand scafolds play an important role in the

chemotherapy, and among ligand system, hydrazones consisting of a carbon–nitro-

gen double bond (R–CO–NH–N=CHR) group [4] belong to special class due to

their interesting multidentate chelating properties and form complexes with almost

all the metal ions in diferent oxidation states depending upon the carbonyl group

and hydrazide der ivatives [5, 6]. They possess div erse biological and pharmaceuti-

cal activities [7, 8 ] suc h as antimicrobial [9, 10], anticancer [11, 12 ] and antioxi-

dant properties [13]. They also show applications in wastewater treatment [14],

1 3

J. Devi et al.

catalytical activity [15 , 16], good magnetic behaviour [17], specifc sensors, non-

linear optical devices [18 ], resin for separation [19] and acting as enzyme inhibitor

[20].

Tetralone, carbonyl entity is selected here for hydrazones’ formation, represents

an important compound in modern medicinal chemistry as it has considerable

importance in biological feld [21], anti-trypanosoma, antidepressant in sertraline

drug, antimalarial [22 ], anticancer, antioxidant [23], anti-infammatory agent [24]

and as inhibitors of monoamine oxidase [25]. As a result to develop ingenious anti-

cancer agent, huge number of transition metal complexes were synthesized from

hydrazones and tested for anticancer activities, and many of them exhibited excel-

lent activities [26]. The literature survey suggested that biological potential of com-

pounds gets inf uenced by the coordination number of metal atom, structure of mol-

ecules and substituents attached to metal atom.

Due to the widespread therapeutic and diagnostic properties of hydrazones

and tetralone derivatives, it seemed appealing to investigate compounds that have

remarkable applications of both antimicrobial and anticancer activities, so here we

have reported the synthesis of hydrazones from condensation of hydrazide deriva-

tives with tetralone and reacted them with transition metal(II) acetates to form

complexes. For characterization and structure determination, various spectroscopic

analyses (UV–Vis, ¹H NMR, ¹³C NMR, FT-IR, mass, ESR and fuorescence), mag-

netic susceptibility, elemental analysis, molar conductance measurements and ther-

mal (TGA, DTG and DTA) methods were used. Screening of compounds for cyto-

toxic activity against three cancer cell lines—human breast adenocarcinoma cell line

(MCF7), human alveolar adenocarcinoma epithelial cell line (A549), human cervi-

cal cell line (HeLa) and Rat myoblast cell line normal (L₆)—were assayed. The anti-

microbial activity was also tested against four bacterial, i.e. (S. aureus, B. subtilis, E.

coli and P. aeruginosa) and two fungal, i.e. (A. niger, C. albicans), strains.

Experimental

Materials

The solvents, chemicals and reagents used for the research were of analytical grade.

Hydrazide derivatives (nicotinic acid, benzoic acid, toluic acid and isonicotinic acid),

α-tetralone and metal(II) acetates [Co(CH₃COO)₂·4H₂O, Ni(CH₃COO)₂·4H₂O,

Cu(CH₃COO)₂·H₂O and Zn(CH₃COO)₂·2H₂O] were purchased from Sigma-Aldrich

company. The solvents used were dried as reported in the literature [27].

Instrumentation

Infrared spectra of hydrazones and their metal complexes were measured by using

KBr pellets on Shimadzu IR afnity-I 8000 FT-IR spectrophotometer within

the range of 400–4000 cm⁻¹. NMR spectra (¹H and ¹³C) of hydrazones and their

zinc(II) complexes were obtained in CDCl₃by taking TMS as an internal reference

1 3

Transition metal (II) complexes of hydrazones derived from…

on Bruker Avance II 400 MHz NMR spectrometer. The coupling constant (J) and

chemical shift (δ) were measured in Hz and ppm. Elemental (CHN) data were ana-

lysed by the instrument PerkinElmer 2400 elemental analyser. Standard gravimetric

procedures were used to determine the metal percentage in the compounds, nickel

as nickel dimethylglyoximate, zinc as zinc ammonium phosphate, cobalt as cobalt

pyridine thiocyanate and copper as cupreous thiocyanate [28]. Electronic spectral

data were obtained in DMSO by using UV–Vis–NIR Varian Cary-5000 spectro-

photometer. ESR spectral analysis of the Cu(II) complexes was measured by tak-

ing tetracyanoethylene (TCNE) free radical as an internal reference on the Varian

E112 X-band spectrometer. Gouy’s procedure is used to calculate the magnetic

susceptibilities of the compounds at 298 K by taking Hg[Co(SCN)₄] as the refer-

ence to calibrate the instrument. Conductivity of 10⁻³M solution was measured by

using a model-306 Systronics conductivity bridge at 298 K in DMSO. The melting

points (°C) of compounds were measured on a hot-stage Gallen Kamp melting point

apparatus in open capillaries. Mass spectra of compounds were obtained by using

API 2000 Applied Bio systems mass spectrometer in DMSO solvent. PerkinElmer

Diamond TG/DTA thermogravimetric analyser is used to carry out thermal (TGA,

DTG and DTA) study of compounds under nitrogen atmosphere with fow rate of

20 mL/min and heating rate 10 °C/min. Steady-state fuorescence spectra of hydra-

zones and their respective complexes were carried out on Shimadzu RF-5301 PC

spectrophotometer.

Pharmacology

Antimicrobial assay

Hydrazones and their respective transition metal complexes were screened for

their in vitro antimicrobial activity against four bacterial species: Bacillus subtilis

(MTCC 8561), Staphylococcus aureus (MTCC 2901), Pseudomonas aeruginosa

(MTCC 424), Escherichia coli (MTCC 16,521) and two fungal species: Candida

albicans (MTCC 227), Aspergillus niger (MTCC 8189) by serial dilution method

[29]. Test organisms were grown on nutrient agar (bacterial strain) and sabouraud

dextrose (fungal strain) as nutrient medium. The stock solution was obtained by add-

ing 2 mg of synthesized compounds in 10 mL DMSO. Further, to prepare a solu-

tion of 100 μg/mL concentration, 1 mL of this stock solution was poured into each

test tube having 1 mL of nutrient broth/sabouraud dextrose broth. The solutions of

50, 25, 12.50 and 6.25 μg/mL concentrations were prepared by the serial dilution

method. Microbial species were grown at 37 °C for 24 h in case of the bacterial and

at 25 °C for one week in case of the fungal strains. Ciprofoxacin is used as a refer-

ence drug for antibacterial and fuconazole for antifungal activity, and their activity

was also performed by taking DMSO as negative control. After incubation, the data

were observed at various concentrations and calculated their MIC values in μ mol/

mL. The microbial activity of compounds was carried out in duplicate to minimize

error, and an average value is reported here.

1 3

J. Devi et al.

Cytotoxic assay

The in vitro anticancer activity of the compounds (1–20) was tested as given by

Mosmann [30]. The cytotoxicity was evaluated against a series of three diferent

human carcinoma cell lines: A549 derived from human alveolar adenocarcinoma

epithelial cell lines (ATCC No.CCL-185), HeLa derived from human cervical ade-

nocarcinoma epithelial cell lines (ATCC No. CCL-2), MCF7 derived from human

breast adenocarcinoma epithelial cell lines (ATCC No.HTB-22) as well as normal

cell line L₆derived from rat skeletal muscle myoblast cells (ATCC No. CRL-1458),

and these cells were cultured in Dulbecco’s modifed Eagle’s medium (DMEM) sup-

plemented with 1% gentamicin, 10% foetal bovine serum (FBS) and 10% Pen-Strep.

Briefy, cells (1×10⁶per mL) were seeded in tissue culture grade multiwall plates

in complete medium and incubated under standard conditions in 37 °C humidifed

5% CO₂atmosphere. The complete medium was replaced after one day with FBS-

free medium and incubated overnight. The cells were then treated with the samples

in various concentrations into each well and incubated for 24 h. Well containing

medium alone (untreated cells) was served as a control. After the incubation period,

10 µL of MTT (5 mg/mL) was poured to each well, mixed thoroughly and incubated

again for 4 h. After the incubation period, cells were seen with the help of inverted

microscope for the existence of dark purple crystals of formazan at the bottom of the

wells. Isopropanol (100 µL) with 0.04 M HCl was poured to each well and mixed it

completely by repeated pipetting with a multi-channel pipette. The HCl converts the

phenol red in tissue culture medium to a yellow colour that does not interfere with

the MTT formazan measurement. The isopropanol dissolves the formazan to give a

homogeneous blue solution suitable for absorbance calculation, and absorbance was

calculated by ELISA plate reader (Filter Max F₃Multi-Mode Micro plate Readers,

Molecular Devices) with a test wavelength of 570 nm and a reference wavelength of

630 nm. The efect of the samples on the proliferation of cells was expressed as the

% inhibition of cell proliferation and measured as (Absorbance of control cells—

Absorbance of treated cells/Absorbance of control cells)×100. Cytotoxic concentra-

tion (IC₅₀) of the samples was calculated by the dose–response curves. The antican-

cer data are mean standard deviation and were taken as the average of three sets of

readings of independent trials by taking doxorubicin as reference drug.

Synthesis

Synthesis of hydrazones (HL¹–HL⁴) (1–4)

The

hydrazones:

HL²/4-methyl-benzoic

nicotinic

acid

(3,4-dihydro-2H-naphthalen-1-ylidene)-

hydrazide HL¹/benzoic acid (3,4-dihydro-2H-naphthalen-1-ylidene)-hydrazide

(3,4-dihydro-2H-naphthalen-1-ylidene)-hydrazide

HL³/isonicotinic acid (3,4-dihydro-2H-naphthalen-1-ylidene)-hydrazide HL⁴

were synthesized by the condensation of tetralone (0.438 g, 3.0 mmol) with nic-

otinic (0.411 g) HL¹/benzoic (0.408 g) HL²/p-toluic (0.450 g) HL³/isonicotinic

(0.411 g) HL⁴acid hydrazide (3.0 mmol) under refuxing in ethanol (20 mL) for

1 3

Transition metal (II) complexes of hydrazones derived from…

O

C

H

N

Ar

NH₂

Reflux 2-4 h Ar

MeOH

N

+

tutomerism

N

H

C

N

Ar

C

O

N

OH

O

N

L¹

=

5, 9, 13, 17

=

[Co(L^1-4)₂(H₂O)₂]

=

Ar

1.

6, 10, 14, 18 = [Ni(L^1-4)₂(H₂O)₂]

2. L²= Ar =

H₃C

Ar

N

C

O

N

M

N

3. L³= Ar =

7, 11, 15, 19 = [Cu(L^1-4)₂(H₂O)₂]

8, 12, 16, 20 = [Zn(L^1-4)₂(H₂O)₂]

H₂O

OH₂

Ar

4. L⁴= Ar =

N

O

C

N

M= Co(II), Ni(II), Cu(II) and Zn(II)

Scheme 1 Synthesis of hydrazones (1–4) and their transition metal complexes (5–20)

2–4 h in equimolar ratio under constant stirring. The reaction progress was regularly

monitored by TLC. The light colour solid compounds were separated by fltration,

washed with methanol, dried under vacuum over anhydrous calcium chloride, and

recrystallized from chloroform to obtain pure hydrazones (Scheme 1).

Nicotinic acid (3,4‑dihydro‑2H‑naphthalen‑1‑ylidene)‑hydrazide (HL¹)

Yield: 87%; Colour: Light yellow; M.p.: 75–78 °C; Conductivity:

(ohm⁻¹cm²mol⁻¹) in DMSO: 12; C₁₆H₁₅N₃O: Anal. Cald: C, 72.43; H, 5.70;

N, 15.84, Found: C, 72.42; H, 5.73; N, 15.87; MS: m/z (M⁺) Cald: 265.31;

Found:266.7077 (M + 1)⁺; FT-IR (KBr, ν, cm⁻¹): 1653 ν(C=O, carbonyl), 3258

ν(–NH),1615 ν(–C=N), 1013 ν(–N–N–H); ¹H NMR [400 MHz, CDCl₃, δ(ppm)]:

′

9.26 (s, t, 1H, N=C–OH), 7.85 (d, J = 4 Hz, 1H, C₅–H), 7.51 (d, J = 8 Hz, 1H,

C₉_′–H), 7.21 (d, J = 8 Hz, 2H, C₆–H), 7.18 (d, J = 8 Hz, 2H, C₇–H), 8.78 (s, 1H,

′

C₂_′–H), 7.36 (t, J = 8 Hz, 1H, C₈–H), 7.25 (t, J = 4 Hz, 1H, C₄–H), 8.30 (s, 2H,

C₃–H), 2.85 (t, J = 6 Hz, 2H, C₄–H), 2.71 (t, J = 6 Hz, 2H, C₂–H), 2.04 (m,

J = 6 Hz, 2H, C₃–H);¹³C NMR:[100 MHz, CDCl₃, δ(ppm)]: 166.38 (HNC=O),

′

151.70 (C₁_′), 139.66 (C₂_′), 131.95 (C₅), 129.94 (C₉), 137.92 (C₅), 122.92 (C₄),

133.90 (C₃), 133.60 (C₁), 128.93 (C₈), 126.61 (C₆), 124.21 (C₇), 120.12 (C₁₀),

29.93 (C₄), 24.58 (C₂), 21.27 (C₃).

1 3

J. Devi et al.

Benzoic acid (3,4‑dihydro‑2H‑naphthalen‑1‑ylidene)‑hydrazide (HL²)

Yield: 82%; Colour: white; M.p.: 72–75 °C; Conductivity: (ohm⁻¹cm²mol⁻¹)

in DMSO: 11, C₁₇H₁₆N₂O: Anal. Cald: C, 77.25; H, 6.10; N, 10.60, Found.:

C, 77.22; H, 6.08; N, 10.58, MS: m/z (M⁺) Cald: 264.12; Found:265.1241

(M + 1)⁺; FT-IR (KBr, ν, cm⁻¹): 1648 ν(C=O, carbonyl), 3242 ν(–NH),1612

1

ν(–C=N), 1013 ν(–N–N–H); H NMR [400 MHz, CDCl₃, δ(ppm)]: 9.01 (s, H,

′

N=C–OH), 8.38 (s, 1H, C₉–H), 7.89 (d, 2H, J = 12 Hz, C₂–H and C₆–H), 7.59

′

(t, J = 12 Hz, 1H, C₄–H), 7.52 (t, J = 12 Hz, 2H, C₃–H and C₅–H), 7.28 (d,

1H, C₈–H. J = 8 Hz), 7.16 (d, J = 8 Hz,2H, C₆–H and C₇–H), 2.85 (t, J = 6 Hz,

2H, C₄–H), 2.68 (t, J = 6 Hz, 2H, C₂–H), 2.03 (m, J = 6 Hz, 2H, C₃–H); ¹³C

NMR:[100 MHz, CDCl₃, δ(ppm)]: 161.31 (HNC=O), 150.62 (C₁), 139.63 (C₅),

′

135.93 (C₁_′), 128.12 (C₉), 131.27 (C₂), 129.17 (C₆), 133.61 (C₄), 130.59 (C₃),

127.88 (C₅), 126.61 (C₈), 125.55 (C₆), 125.25 (C₇), 121.18 (C₁₀), 29.62 (C₄),

25.25 (C₂), 21.61 (C₃).

4‑Methyl‑benzoic acid (3,4‑dihydro‑2H‑naphthalen‑1‑ylidene)‑hydrazide (HL³)

Yield: 79%; Colour: white; M.p.: 74–76 °C; Conductivity: (ohm⁻¹cm²mol⁻¹)

in DMSO: 12; C₁₈H₁₈N₂O: Anal. Cald: C, 77.67; H, 6.52; N, 10.06, Found.: C,

77.65; H, 6.50; N, 10.05, MS: m/z (M⁺) Cald: 278.15; Found:279.1575 (M + 1)⁺;

FT-IR (KBr, ν, cm⁻¹): 1645 ν(C = O, carbonyl), 3246 ν(–NH),1610 ν(–C = N),

1015 ν(–N–N–H); ¹H NMR [400 MHz, CDCl₃, δ(ppm)]: 9.04 (s, ¹H, N = C–OH),

′

8.37 (s, 1H, C₉–H), 7.31 (d, J = 8.4 Hz, 2H, C₂–H and C₆–H), 7.28 (d, J = 8.4 Hz,

′

2H, C₃–H and C₅–H), 7.81 (t, J = 8 Hz, 1H, C₈–H), 7.16 (d, J = 8 Hz, 2H, C₆–H

and C₇–H), 2.85 (t, J = 6.0 Hz, 2H, C₄–H), 2.67 (t, J = 6 Hz, 2H, C₂–H), 2.04 (m,

J = 6 Hz, 2H, C₃–H), 2.45 (s, 3H, –CH₃); ¹³C NMR: [100 MHz, CDCl₃, δ(ppm)]:

′

163.63 (HNC=O), 153.64 (C₁), 139.92 (C₅), 132.54 (C₁), 130.20, (C₉), 127.90

′

(C₂), 126.23 (C₆), 133.58 (C₄), 128.56 (C₃), 127.58 (C₅), 126.91 (C₈), 124.57

(C₆), 123.88 (C₇), 122.24 (C₁₀), 29.62 (C₄), 23.29 (-CH₃), 25.17 (C₂), 21.58 (C₃).

Isonicotinic acid (3,4‑dihydro‑2H‑naphthalen‑1‑ylidene)‑hydrazide (HL⁴)

Yield: 78%; Colour: white; M.p.: 77–79 °C; Conductivity: (ohm⁻¹cm²mol⁻¹)

in DMSO: 13.; C₁₆H₁₅N₃O: Anal. Cald: C, 72.43; H, 5.71; N, 15.85, Found.: C,

72.42; H, 5.73; N, 15.87; MS: m/z (M⁺) Cald: 265.12; Found: 266.1277 (M + 1)⁺;

FT-IR (KBr, ν, cm⁻¹): 1655 ν(C=O, carbonyl), 3248 ν(–NH),1611 ν(–C = N),

1

1018 ν(–N–N–H); H NMR [400 MHz, CDCl₃, δ(ppm)]: 9.86 (s, H, N=C–OH),

′

8.24 (s, 1H, C₉–H), 7.66 (d, J = 8 Hz, 2H, C₂–H and C₅–H), 8.67 (d, J = 8 Hz,

′

2H, C₃–H and C₄–H), 7.06 (t, J = 6.2 Hz, 1H, C₈–H), 7.16 (d, J = 6.2 Hz, 2H,

C₆–H and C₇–H), 2.85 (t, J = 6 Hz, 2H, C₄–H), 2.71 (t, J = 6, Hz, 2H, C₂–H),

2.04 (m, J = 6 Hz, 2H, C₃–H); ¹³C NMR:[100 MHz, CDCl₃, δ(ppm)]: 162.37

′

(HNC=O), 147.15 (C₁), 142.99 (C₅), 133.22(C₁), 126.85(C₉), 128.55 (C₂),

′

131.26 (C₃), 130.22 (C₄), 128.23 (C₅), 129.24 (C₈), 127.20 (C₆), 123.90 (C₇),

121.17 (C₁₀), 29.61 (C₄), 26.79(C₂), 21.58 (C₃).

1 3

Transition metal (II) complexes of hydrazones derived from…

Synthesis of transition metal complexes [M(L^1–4)₂(H₂O)₂] (5–20)

To the methanolic solution (20 mL) of metal acetates [M(CH₃COO)₂·xH₂O]

of cobalt (0.248 g, 1.0 mmol)/nickel (0.248 g, 1.0 mmol)/copper (0.198 g,

1.0 mmol)/zinc (0.220 g, 1.0 mmol) was added a hot aqeuous methanolic solu-

tion (20 mL) of hydrazones HL¹(0.530 g, 2.0 mmol)/HL²( 0.528 g, 2.0 mmol)/

HL³(0.556 g, 2.0 mmol)/HL⁴(0.530 g, 2.0 mmol) with constant stirring in 1:2

molar ratio for 2–3 h. To maintain the pH of the solution, NaOH was added to it.

The separated compounds were fltered, recrystallized with methanol and washed

with hexane to separate out unreacted metal acetates to obtain pure product

(Scheme 1).

Co(L¹)₂(H₂O)₂]

Yield: 73%; Colour: Reddish brown; M.p.: 180–85 °C; Conductivity:

(ohm⁻¹cm²mol⁻¹) in DMSO: 17; C₃₂H₃₂CoN₆O₄; Anal. Cald: C, 61.63; H,

5.18; N, 13.45, Co, 9.46;Found.: C, 61.64; H, 5.17; N, 13.48; MS: m/z (M⁺)

Cald: 623.5982; Found:624.5712 (M + 1)⁺; FT-IR (KBr, ν, cm⁻¹): 1253 ν(C–O),

3427 ν(coordinated water),1598 ν(–C=N), 1018 ν(–N–N–H), 545 ν(Co–O), 435

ν(Co–N).

[Ni(L¹)₂(H₂O)₂]

Yield: 75%; Colour: Green; M.p.: 197–99 °C; Conductivity: (ohm⁻¹cm²mol⁻¹)

in DMSO: 12; C₃₂H₃₂NiN₆O₄; Anal. Cald: C, 61.69; H, 5.48; N, 13.43, Ni, 9.40;

Found.: C, 61.66; H, 5.17; N, 13.48; MS: m/z (M⁺) Cald: 623.3573; Found:

624.3307 (M+1)⁺; FT-IR (KBr, ν, cm⁻¹): 1245 ν(C-O), 3425 ν(coordinated

water),1594 ν(–C=N), 1021 ν(–N–N–H), 547 ν(Ni–O), 440 ν(Ni–N).

[Cu(L¹)₂(H₂O)₂]

Yield: 78%; Colour: Brown; M.p.: 194–97 °C; Conductivity: (ohm⁻¹cm²mol⁻¹) in

DMSO: 18; C₃₂H₃₂CuN₆O₄; Anal. Cald: C, 61.19; H, 5.13; N, 13.35, Cu, 10.09;

Found.: C, 61.18; H, 5.13; N, 13.38, MS: m/z (M⁺) Cald: 628.2035; Found:629.1889

(M+1)⁺; FT-IR (KBr, ν, cm⁻¹): 1248 ν(C-O), 3428 ν(coordinated water),1595

ν(–C=N), 1023 ν(–N–N–H), 543 ν(Cu–O), 442 ν(Cu–N).

[Zn(L¹)₂(H₂O)₂]

Yield: 76%; Colour: Reddish brown; M.p.: 192–95 °C; Conductivity:

(ohm⁻¹cm²mol⁻¹) in DMSO: 19; C₃₂H₃₂ZnN₆O₄; Anal. Cald: C, 61.02; H, 5.11;

N, 13.31, Zn:10.38; Found.: C, 61.00; H, 5.12; N, 13.34; MS: m/z (M⁺) Cald:

630.0549; Found: 631.0265 (M+1)⁺; FT-IR (KBr, ν, cm⁻¹): 1233 ν(C–O), 3430

ν(coordinated water),1586 ν(–C=N), 1029 ν(–N–N–H), 548 ν(Zn–O), 439 ν(Zn–N),

′

¹H NMR [400 MHz, CDCl₃, δ(ppm)]: 7.85 (d, J=4 Hz, 1H, C₅–H), 7.51 (d,

1 3

J. Devi et al.

′

J=8 Hz, 1H, C₉–H), 8.52 (d, J=8 Hz, 1H, C₂–H), 7.25 (t, J=4 Hz, 1H, C₄–H),

′

8.07 (s, 2H, C₃–H); 7.35 (t, J=8 Hz, 1H, C₈–H), 7.21 (d, J=8 Hz, 2H, C₆–H),

7.18 (d, J=8 Hz, 2H, C₇–H), 2.86 (t, J=6.2 H, 2H, C₄–H), 2.70 (t, J=5.2 Hz, 2H,

C₂-H), 2.44 (s, 2H, H₂O), 2.04 (m, J=6.8 Hz, 2H, C₃-H); ¹³C NMR:[ 100 MHz,

′

CDCl₃, δ(ppm)]: 169.02 (N=C–OH), 152.79 (C₁), 139.60 (C₂), 131.93 (C₅), 129.84

′

(C₉), 137.94 (C₅), 122.92 (C₄), 133.91 (C₃), 133.62 (C₁), 128.97 (C₈), 126.62 (C₆),

124.22 (C₇), 120.16 (C₁₀), 29.96 (C₄), 24.23 (C₂), 21.35(C₃).

[Co(L²)₂(H₂O)₂]

Yield: 77%; Colour: Reddish brown; M.p.: 195–97 °C; Conductivity:

(ohm⁻¹cm²mol⁻¹) in DMSO: 16; C₃₄H₃₄CoN₄O₄; Anal. Cald: C, 65.72; H, 5.51; N,

9.04; Co, 9.45; Found.: C, 65.70; H, 5.51; N, 5.01, MS: m/z (M⁺) Cald: 621.3527;

Found:622.6552 (M+1)⁺; FT-IR (KBr, ν, cm⁻¹): 1249 ν(C–O), 3417 ν(coordinated

water),1591 ν(–C=N), 1016 ν(–N–N–H), 540 ν(Co–O), 426 ν(Co–N).

[Ni(L²)₂(H₂O)₂]

Yield: 79%; Colour: Green; M.p.: 227–32 °C; Conductivity: (ohm⁻¹cm²mol⁻¹)

in DMSO: 14; C₃₄H₃₄NiN₄O₄; Anal. Cald: C, 65.71; H, 5.51; N, 9.04; Ni, 9.43;

Found.: C, 65.72; H, 5.52; N, 9.02; MS: m/z (M⁺) Cald: 621.5978; Found: 622.6252

(M+1)⁺; FT-IR (KBr, ν, cm⁻¹): 1267, ν(C-O), 3415 ν(coordinated water),1588

ν(–C=N), 1017 ν(–N–N–H), 542 ν(Ni–O), 422 ν(Ni–N).

[Cu(L²)₂(H₂O)₂]

Yield: 72%; Colour: Brown; M.p.: 216–19 °C; Conductivity: (ohm⁻¹cm²mol⁻¹)

in DMSO: 17; C₃₄H₃₄CuN₄O₄; Anal. Cald: C, 65.23; H, 5.48; N, 8.92,Cu, 10.12;

Found.: C, 65.21; H, 5.47; N, 8.92; MS: m/z (M⁺) Cald: 627.2047; Found:628.2396

(M+1)⁺; FT-IR (KBr, ν, cm⁻¹): 1248 ν(C–O), 3422 ν(coordinated water),1589

ν(–C=N), 1018 ν(–N–N–H), 539 ν(Cu–O), 425 ν(Cu–N).

[Zn(L²)₂(H₂O)₂]

Yield: 75%; Colour: Reddish brown; M.p.: 218–22 °C; Conductivity:

(ohm⁻¹cm²mol⁻¹) in DMSO: 20; C₃₄H₃₄ZnN₆O₄; Anal. Cald: C, 65.04; H,

5.45; N, 8.92, Zn; 10.38; Found.: C,65.02; H,5.46; N, 8.91; MS: m/z (M⁺) Cald:

628.0767; Found:629.0546 (M+1)⁺; FT–IR (KBr, ν, cm⁻¹): 1253 ν(C–O), 3425,

ν(coordinated water),1585 ν(–C=N), 1019 ν(–N–N–H), 537 ν(Zn–O), 427 ν(Zn–N);

¹H NMR [400 MHz, CDCl₃, δ(ppm)]: 8.32 (d, 1H, C₉–H), 7.88 (d, J=12, Hz 2H,

′

C₂_′–H and C₆–H), 7.61 (t, J=12 Hz, 1H, C₄–H), 7.52 (t, J=12 Hz, 2H, C₃–H and

C₅–H), 7.28 (d, J=8 Hz, 1H, C₈–H), 7.16 (d, J=8 Hz, 2H, C₆–H and C₇–H), 2.84

(t, J=6 Hz, 2H, C₄–H), 2.68 (t, J=6 Hz, 2H, C₂–H), 2.03 (m, J=6 Hz, 2H, C₃–H),

1 3

Transition metal (II) complexes of hydrazones derived from…

2.40 (s, 2H, H₂O); ¹³C NMR:[100 MHz, CDCl₃, δ(ppm)]: 164.02 (N=C–OH),

′

153.63(C₁), 142.26 (C₅), 135.95(C₁), 128.54 (C₉), 131.94 (C₂), 129.91 (C₆), 133.23

′

(C₄), 130.60 (C₃), 127.58 (C₄), 126.61 (C₈), 125.55 (C₆), 125.25 (C₇), 121.19 (C₁₀),

29.63 (C₄), 25.23 (C₂), 20.28 (C₃).

[Co(L³)₂(H₂O)₂]

Yield: 73%; Colour: Reddish brown; M.p.: 178–181 °C; Conductivity:

(ohm⁻¹cm²mol⁻¹) in DMSO: 13; C₃₆H₃₈CoN₄O₄; Anal. Cald: C: 66.55; H: 5.92; N,

8.65, Co, 9.04; Found.: C, 66.56; H, 5.90; N, 8.62; MS: m/z (M⁺) Cald: 649.6586;

Found:650.2863 (M+1)⁺; FT-IR (KBr, ν, cm⁻¹): 1262, ν(C–O), 3431 ν(coordinated

water),1599 ν(–C=N), 1021 ν(–N–N–H), 547 ν(Co–O), 434, ν(Co–N).

[Ni(L³)₂(H₂O)₂]

Yield: 75%; Colour: Green; M.p.: 214–218 °C; Conductivity: (ohm⁻¹cm²mol⁻¹)

in DMSO: 16; C₃₆H₃₈NiN₄O₄; Anal. Cald: C, 66.57; H, 5.91; N, 8.60,,Ni, 9.01;

Found.: C, 66.58; H, 5.90; N, 8.63; MS: m/z (M⁺) Cald: 649.4219.; Found:650.4258

(M+1)⁺; FT-IR (KBr, ν, cm⁻¹): 1225 ν(C–O), 3434, ν(coordinated water),1590

ν(–C=N), 1023 ν(–N–N–H), 540 ν(Ni–O), 435 ν(Ni–N).

[Cu(L³)₂(H₂O)₂]

Yield: 78%; Colour: Brown; M.p.: 192–96 °C; Conductivity: (ohm⁻¹cm²mol⁻¹)

in DMSO: 17; C₃₆H₃₈CoN₆O₄; Anal. Cald: C, 66.07; H, 5.84; N, 8.56;Cu, 9.69;

Found.: C, 66.09; H, 5.85; N, 8.51; MS: m/z (M⁺) Cald: 654.3189; Found:655.4115

(M+1)⁺; FT-IR (KBr, ν, cm⁻¹): 1234 ν(C–O), 3437 ν(coordinated water),1591

ν(–C=N), 1025 ν(–N–N–H), 554 ν(Cu–O), 437 ν(Cu–N).

[Zn(L³)₂(H₂O)₂]

Yield: 76%; Colour: white; M.p.: 193–93 °C; Conductivity: (ohm⁻¹cm²mol⁻¹)

in DMSO: 18; C₃₆H₃₈CoN₆O₄; Anal. Cald: C, 65.92; H, 5.83; N, 8.51, Zn:9.71;

Found: C, 65.90; H, 5.84; N, 8.54; MS: m/z (M⁺) Cald: 656.1274; Found:657.1084

(M+1)⁺; FT-IR (KBr, ν, cm⁻¹): 1255 ν(C–O), 3435 ν(coordinated water),1592

1

ν(–C=N), 1024 ν(–N–N–H), 550 ν(Zn–O), 431 ν(Zn–N); H NMR [400 MHz,

′

CDCl₃, δ(ppm)]:. 8.21(d, J=8 Hz, 1H, C₉–H), 7.30 (t, J=8.4 Hz, 1H, C₄–H and

′

C₂–H), 7.28 (d, J=8.4 Hz, 2H, C₃–H and C₅–H), 7.62 (t, J=8 Hz, 1H, C₈–H), 7.16

(d, J=8 Hz, 2H, C₆–H and C₇–H), 2.85 (t, J=6 Hz, 2H, C₄–H), 2.67 (t, J=6 Hz,

2H, C₂–H), 2.03 (m, J=6 Hz, 2H, C₃–H), 2.46 (s, 3H, –CH₃), 2.38 (s, 2H, H₂O);

¹³C NMR:[100 MHz, CDCl₃, δ(ppm)]: 165.37 (N=C–OH), 154.62 (C₁), 143.61

′

(C₅_′), 132.54 (C₁), 130.20, (C₉), 127.90 (C₂), 126.23 (C₆), 133.58 (C₄), 128.56

′

(C₃), 129.74 (C₄), 127.98 (C₅), 126.91 (C₈), 124.44 (C₆), 123.86 (C₇), 122.25 (C₁₀),

29.62 (C₄), 23.19 (–CH₃), 25.27 (C₂), 21.58 (C₃).

1 3

J. Devi et al.

[Co(L⁴)₂(H₂O)₂]

Yield: 75%; Colour: Reddish brown; M.p.: 213–16 °C; Conductivity:

(ohm⁻¹cm²mol⁻¹) in DMSO: 15; C₃₂H₃₂CoN₆O₄; Anal. Cald: C, 61.61; H, 5.15; N,

13.49, Co, 9.43; Found.: C, 61.64; H, 5.17; N, 13.48; MS: m/z (M⁺) Cald: 625.1068;

Found:626.1076 (M+1)⁺; FT-IR (KBr, ν, cm⁻¹): 1253 ν(C–O), 3437 ν(coordinated

water),1588 ν(–C=N), 1018 ν(–N–N–H), 545 ν(Co–O), 442 ν(Co–N).

[Ni(L⁴)₂(H₂O)₂]

Yield: 74%; Colour: Green; M.p.: 242–46 °C; Conductivity: (ohm⁻¹cm²mol⁻¹) in

DMSO: 17; C₃₂H₃₂NiN₆O₄; Anal. Cald: C, 61.67; H, 5.20; N, 13.49, Ni, 9.44; Found.:

C, 61.66; H, 5.17; N, 13.48; MS: m/z (M⁺) Cald: 625.1768; Found:626.3393 (M+1)⁺;

FT-IR (KBr, ν, cm⁻¹): 1232 ν(C–O), 3440 ν(coordinated water),1584 ν(–C=N), 1021

ν(–N–N–H), 546 ν(Ni–O), 436 ν(Ni–N).

[Cu(L⁴)₂(H₂O)₂]

Yield: 77%; Colour: Brown; M.p.: 223–28 °C; Conductivity: (ohm⁻¹cm²mol⁻¹) in

DMSO: 18; C₃₂H₃₂CoN₆O₄; Anal. Cald: C, 61.20; H, 5.15; N, 13.37,Cu, 10.14; Found.:

C, 61.18; H, 5.13; N, 13.38; MS: m/z (M⁺) Cald: 628.1557; Found:629.4533 (M+1)⁺;

FT-IR (KBr, ν, cm⁻¹): 1228 ν(C–O), 3448 ν(coordinated water),1593 ν(–C=N), 1023

ν(–N–N–H), 543 ν(Cu–O), 440 ν(Cu–N).

[Zn(L⁴)₂(H₂O)₂]

Yield: 79%; Colour: white; M.p.: 230–33 °C; Conductivity: (ohm⁻¹cm²mol⁻¹)

in DMSO: 19; C₃₂H₃₄CoN₆O₄; Anal. Cald: C, 61.03; H, 5.14; N, 13.33, Zn: 10.40;

Found.: C, 61.00; H, 5.12; N, 13.34; MS: m/z (M⁺) Cald: 630.0523; Found:631.1550

(M+1)⁺; FT-IR (KBr, ν, cm⁻¹): 1253 ν(C–O), 3446 ν(coordinated water),1596

1

ν(–C=N), 1029 ν(–N–N–H), 547 ν(Zn–O), 445 ν(Zn–N); H NMR [400 MHz,

′

CDCl₃, δ(ppm)]: 8.03 (s, 1H, C₉–H), 7.66 (d, J=8 Hz, 2H, C₂–H and C₅–H), 8.66 (d,

′

J=8 Hz, 2H, C₃–H and C₄–H), 7.06 (t, J=6.2 Hz, 1H, C₈–H), 7.16 (d, J=6.2 Hz, 2H,

C₆–H and C₇–H), 2.85 (t, J=6 Hz, 2H, C₄–H), 2.68 (t, J=6 Hz, 2H, C₂–H), 2.04 (m,

J=6 Hz, 2H, C₃–H), 2.40 (s, 2H, H₂O); ¹³C NMR:[100 MHz, CDCl₃, δ(ppm)]: 166.34

′

(N=C–OH), 149.63 (C₁), 142.95(C₅), 133.22(C₁), 126.85(C₉), 128.55 (C₂), 131.26

′

(C₃), 130.22 (C₄), 128.23 (C₅), 129.24 (C₈), 127.20 (C₆), 123.90 (C₇), 121.17 (C₁₀),

29.61 (C₄), 26.31(C₂), 21.28 (C₃).

Results and discussion

The hydrazones were synthesized by the condensation of respective hydrazide deriva-

tive with tetralone in equimolar ratio under refuxing in ethanol, and their transition

metal complexes were obtained by reacting with Co(II), Ni(II), Cu(II) and Zn(II)

1 3

Transition metal (II) complexes of hydrazones derived from…

1 3

J. Devi et al.

acetates at constant stirring in molar ratio 2:1. All the compounds were soluble in

MeOH, CDCl₃and DMSO but were insoluble in water. The hydrazones and transi-

tion metal complexes (1–20) were characterized by various spectroscopic techniques

(NMR, Mass, FT-IR, ESR, electronic, fuorescence), which suggests octahedral geom-

etry of complexes formulated as [M(L¹⁻⁴)₂(H₂O)₂] where hydrazones get bonded to

metal centre through the nitrogen of (C=N) and oxygen of carbonyl group in enolic

form. The compounds were stable in air, diferently coloured solid, obtained in good

yield and non-electrolytic in nature as their molar conductance values are in range

11–20 Ω⁻¹cm²mol⁻¹[31]. The analytical data are depicted in experimental part and in

Table 1 given in supplementary data.

(

)

(

) (

)

M CH₃COO ⋅ xH₂O + HL¹⁻⁴→ [M L¹⁻⁴H₂O ] + 2CH₃COOH

2

where M=Co(II), Ni(II), Cu(II) and Zn(II).

IR spectra of compounds

The FT-IR spectral analysis of compounds was obtained in 400–4000 cm⁻¹region

by using KBr pellets. The bands of hydrazones and their respective complexes tabu-

lated in Table 2 given in supplementary data and experimental part were compared

with each other to confrm the coordination sites on the basis of the shifts in the

Table 2 Characteristic IR frequencies ν(cm⁻¹) of hydrazones and their respective transition metal(II)

complexes

C. no. Compounds

ν(–HOH)

ν(C=O)

ν(–C=N)

ν(N–H) ν(N–N–H)

ν(M–O) ν(M–N)

water

amide

1

2

3

4

5

6

7

8

HL¹

HL²

HL³

HL⁴

–

1653

1648

1645

1655

–

1615

1612

1610

1613

1598

1594

1595

1586

1591

1588

1589

1585

1599

1590

1591

1592

1588

1584

1593

1596

3258

3242

3246

3248

–

1013

1011

1015

1018

1017

1021

1023

1029

1016

1017

1018

1019

1021

1023

1025

1024

1021

1026

1025

–

[Co(L¹)₂(H₂O)₂] 3427

[Ni(L¹)₂(H₂O)₂]

3425

[Cu(L¹)₂(H₂O)₂] 3428

[Zn(L¹)₂(H₂O)₂]

3430

[Co(L²)₂·(H₂O)₂] 3417

[Ni(L²)₂(H₂O)₂]

3415

[Cu(L²)₂(H₂O)₂] 3422

[Zn(L²)₂(H₂O)₂]

3425

[Co(L³)₂(H₂O)₂] 3431

[Ni(L³)₂(H₂O)₂]

3434

[Cu(L³)₂(H₂O)₂] 3437

545

547

543

548

540

542

539

537

547

540

554

550

545

546

543

547

435

440

442

439

426

422

425

427

434

435

437

431

442

436

440

445

9

10

11

12

13

14

15

16

17

18

19

20

[Zn(L³)₂(H₂O)₂]

3435

[Co(L⁴)₂(H₂O)₂] 3437

[Ni(L⁴)₂·(H₂O)₂] 3440

[Cu(L⁴)₂(H₂O)₂] 3448

–

[Zn(L⁴)₂(H₂O)₂]

3446

1 3

Transition metal (II) complexes of hydrazones derived from…

absorbance frequency of diferent types of groups and the absence of certain absorp-

tion band due to changes in the electronic environment of the hydrazones after com-

plexation. A strong band in ligands at 1615–1610 cm⁻¹due to azomethine group

shifts to the lower-frequency region 1599–1584 cm⁻¹on complexation with the

metal atom; this downfeld shifting sho ws the bonding via lone pair of the nitrogen

of (C=N) group to metal centre [32, 33]. The bands in the region 1655–1645 cm⁻¹

due to υ(C=O) group and at 3258–3242 cm⁻¹due to υ(N–H) group in Schif base

hydrazones got disappeared, indicating their enolization and chelation with metal

centre. The shifting of υ(N–N-H) band at 1018–1011 cm⁻¹in free hydrazone to

higher value 1029–1016 cm⁻¹in the transition metal complexes confrmed the

coordination via lone pair electron of the nitrogen to the metal centre. The appear-

ance of new sharp and distinct bands in the far-infrared spectra of all complexes

at 554–537 cm⁻¹and 445–422 cm⁻¹, due to M–O and M–N bonds, suggests the

coordination of metal with oxygen and nitrogen atoms [34]. A broad peak near

3448–3415 cm⁻¹is due to stretching vibration of water molecules coordinated to

the central metal ion [35]. From the above IR data, it is suggested that hydrazones

are bidentate (NO) in nature, and they bind with the metal ion through a nitrogen of

(C=N) group and oxygen of carbonyl group.

NMR spectra of compounds

¹H NMR spectra

3

1

3'

4

3'

4

3'

3

4

H₃C

4'

5'

2'

1'

2'

1'

N

5'

2'

1'

4

2'

1'

3'

4'

5'

2

5

2

5

N

4'

2

10

5

8

10

6

10

6

7

6

7

N

1

N

C

N

7

1

C

N

C

N

7

1

10

9

6'

5'

9

8

9

OH

9

8

OH

HL³

OH

HL¹

8

OH

HL⁴

HL²

NMR spectra of hydrazones and their zinc(II) complexes were obtained in CDCl₃,

and their δ values are presented in "experimental" section and Table 3 given in sup-

plementary data. The binding sites (NO) of the hydrazones were con frmed by cor-

relating spectra of ligands with respective zinc complexes. The hydrazones (1–4)

exhibit a singlet at δ 9.86–8.88 ppm due to (–NH) proton which gets disappeared

upon complexation, and the proton loss on the nitrogen indicated deprotonation

of –NH group due to the presence of keto-enol tautomerism on coordination with

the transition metal ion. The metal binds through nitrogen of (C=N) and oxygen

of deprotonated carbonyl oxygen in enolized form showing bidentate nature of

hydrazones, which was also supported with the IR spectra results [36]. The aro-

matic protons were recognized in the range δ 8.78–7.06 ppm, which exhibits only

minor change in the complexes as a result of binding with the metal ion [37]. A

sharp singlet of the three hydrogen atoms of the methyl group at 2.45 ppm in HL³

ligand remains almost unaltered on complexation. The signals due to CH₂group of

1 3

J. Devi et al.

1 3

Transition metal (II) complexes of hydrazones derived from…

1 3

J. Devi et al.

aliphatic ring protons of C₂, C₃, and C₄carbon are in the range δ 2.85–2.04 ppm,

which stands almost unaltered on complexation.

¹³C NMR spectra

The ¹³C NMR spectra of hydrazones showed that characteristic signals at δ

166.38–161.31 ppm due to (HNC=O) carbon, which display upward shifting in

the complexes, indicated the coordination of oxygen atom through lone pair elec-

trons of carbonyl group to the metal ion and the upfeld shifting of C₁carbon of

(C=N) group from δ 153.64–147.15 to δ 154.62–149.63 ppm reveals the coordina-

tion of lone pair of nitrogen to the metal ion centre. The peaks of aromatic carbons

in hydrazones were found near δ 142.99–120.12 ppm, which exhibited only small

alteration upon coordination with transition metal ion. The signal due to carbon of

(–CH₃) in HL³ligand was observed near δ 23.29 ppm and remains unaltered upon

complexation. The signals at δ 29.93–21.27 ppm due to the aliphatic ring C₂, C₃,

and C₄carbons remain almost unchanged. All peak values (¹H NMR and ¹³C NMR)

and their graph related to synthesized ligands and their Zn(II) complexes are given

in supplementary data.

Mass spectra of compounds

The mass spectra of the hydrazones and their metal complexes were obtained and

are specifed in analytical Table 1, and their molecular ion peaks are in agreement

with the expected molar weight values. The mass spectrum provides valuable infor-

mation about the molar weight and structure of com pounds. The mass fragmenta-

tion of the ligand HL⁴(4) is depicted in Fig. 1 and Scheme 2. The mass spectra

show that a molecular ion peak of high intensity at m/z=266.1277 is assigned for

[M+1]⁺, which shows two fragmentation paths where one path shows a peak value

at m/z=189.1113 due to loss of pyridine moiety followed by mass spectrum peak at

m/z=161.0964 due to loss of CO group and at m/z=145.0761 by loss of NH group.

Another fragmentation path depicts peaks at m/z=139.0648 due to loss of pyridine

ring and aromatic ring followed by m/z=111.0568 due to loss of CO group.

In the mass spectra of [Co(L⁴)₂(H₂O)₂] (17) the molecular ion peak at

m/z=626.1076 due to [M+1]⁺is observed, which agrees with its molecular weight

which are described in Fig. 2. The molecular ion peak obtained at m/z=587.1855 is

due to loss of both water molecules coordinated to the transition metal. The peak at

m/z 266.1624 is due to loss of one ligand moiety and cobalt metal itself (Scheme 3)

and after this complex follows the similar fragmentation pattern as hydrazone HL⁴.

Based upon the above mass spectral results, all the transition metal complexes

follow the similar fragmentation model. The molecular ion peaks obtained from

mass spectra were found to be in good agreement with the expected values of the

elemental analysis. The mass spectra of all the hydrazones and their metal com-

plexes indicate their bidentate nature, and the complexation of hydrazones with cen-

tral metal atom is in 2:1 ratio with molecular formula [M(L¹⁻⁴)₂(H₂O)₂].

1 3

Transition metal (II) complexes of hydrazones derived from…

Fig. 1 Mass spectra of hydrazone HL⁴(4)

1 3

J. Devi et al.

N

NH

-

C

O

N

,

+

-

,

tutomerism

H

NH

+

N

C

O

N

C

N

H

NH

,

C

₁₁H₁₂N₂O

OH

C

O

N

m/z =189.1113 (M+1)

C₇H₁₀N₂O

m/z = 139.0646 (M+1)

C₁₆H₁₅N₃O

m/z = 266.1277(M+1)

-CO

+

NH

H

N

H

N

H

N

C₁₀H₁₂N₂

m/z =161.0954 (M+1)

C₆H₁₀N₂

m/z =111.0586 (M+1)

-NH

+

H

N

C

₁₀H₁₁

N

m/z = 145.0764 (M+1)

Scheme 2 The possible molecular ion fragmentation pattern from the mass spectrum of hydrazone HL⁴

(4)

ESR spectra of compounds

The solid-state ESR analysis of the copper (II) complexes was obtained at RT

(300 K) and LNT (77 K) in DMSO to gather information about stereochemis-

try, bonding nature of ligands and metal ion. From the ESR data, the spin Ham-

iltonian parameters were determined and are summarized in Table 4. The ESR

spectrum of [Cu(L³)₂(H₂O)₂] (15) complex describes a strong band in the upfeld

region, which may be due to tumbling. The trend followed for g tensor values was:

g_||(2.43)>g_⊥(2.14)>g_c(2.0023), suggesting residence of single unpaired electron in

2

the d_{x −y}²orbital of Cu(II) ions in the ground state [38], which is predictable feature

of octahedral geometry around metal ions and g_avwas obtained by the formula: 1/3

1 3

Transition metal (II) complexes of hydrazones derived from…

Fig. 2 Mass spectra of [Co(L⁴)₂(H₂O)₂] (17)

(g_||+2 g_⊥) which were found to be lower than free copper(II) ion λ (832 cm⁻¹). Spin

orbital coupling constant λ is calculated from relation g_av=2(1−2 λ/10Dq), and it

supports the evidence for metal→ligand bond to be covalent in nature, and this was

also confrmed from g_avvalues (2.23) of the complex and the spectral parameters of

Cu(II) complexes are given in Table 4.

The measured anisotropic geometric parameter G and g tensor values indicate the

exchange interactions among the copper(II) ion and may be calculated by utilizing

the subsequent equation G=(g_||−2.0023)/(g_⊥−2.0023) [39]. If G<4, then diferent

types of exchange interactions among the Cu(II) centre are present, and if G>4,

then these exchange interactions were minor. In all these copper complexes, the G

1 3

J. Devi et al.

+

N

O

N

O

H

OH₂

-2H₂O

Co

H₂O

O

N

O

N

C₃₂H₃₂CoN₆O₄

m/z = 626.1076 (M+1) peak

C₃₂H₃₀CoN₆O₂

m/z = 587.1825 (M+1) peak

- one ligand moiety+ Co

HO

N

O

N

NH

C₁₅H₁₅CoN₃O

m/z = 266.1624 (M+1) peak

Scheme 3 The possible molecular ion fragmentation pattern for the complex [Co(L⁴)₂(H₂O)₂] (17)

values were found to be in range 2.96–3.69, indicative of considerable exchange

interactions among the Cu(II) centres in the solid steady state [40].

Electronic spectra of compounds

The electronic spectra of the compounds were carried out in solvent DMSO, and

their band assignments are given in Table 5. The electronic spectra of free hydra-

zones showed a band at 28,278–29,815 cm⁻¹and 31,673–33,745 cm⁻¹attributed

to n→π* and π→π* transitions. Shifting in the value of n→π* transition shows

Table 4 ESR spectral

Cu(II) complexes

g_||

g_⊥

g_av

G

parameters of Cu(II) complexes

[Cu(L¹)₂(H₂O)₂]

[Cu(L²)₂(H₂O)₂]

[Cu(L³)₂(H₂O)₂]

[Cu(L⁴)₂(H₂O)₂]

2.40

2.43

2.41

2.44

2.11

2.14

2.12

2.15

2.20

2.23

2.21

2.24

3.69

3.10

3.46

2.96

1 3

Transition metal (II) complexes of hydrazones derived from…

Table 5 Electronic spectral data and magnetic moment (BM) of hydrazones and their transition metal(II)

complexes

Compounds Ligand/Complex Band assignment Transitions

μ_ef(BM) Geometry

1

2

3

4

5

[HL¹]

[HL²]

[HL³]

[HL⁴]

31,698

29,247

31,673

28,278

33,745

29,815

32,689

29,231

π→π*

n→π*

π→π*

n→π*

π→π*

n→π*

π→π

n→π*

–

[Co(L¹)₂(H₂O)₂] 23,531

⁴T_1g(F)→⁴T_1g(P) (v₁)

⁴T_1g(F)→⁴A_2g(F) (v₂)

⁴T_1g(F)→⁴T_2g(F) (v₃)

³A_2g(F)→³T_2g(F) (v₁)

³A_1g(F)→³T_1g(F) (v₂)

³A_2g(F)→³T₁g(P) (v₃)

²B_1g→²A_1g(v₁)

²B_1g→²E_2g(v₂)

LMCT

4.70

Octahedral

17,745

9577

24,345

18,332

10,467

6

7

[Ni(L¹)₂(H₂O)₂]

3.00

1.91

Octahedral

[Cu(L¹)₂(H₂O)₂] 24,156

15,823

8

9

[Zn(L¹)₂(H₂O)₂]

24,456

–

4.60

Octahedral

[Co(L²)₂(H₂O)₂] 23,423

⁴T_1g(F)→⁴T_1g(P) (v₁)

⁴T_1g(F)→⁴A_2g(F) (v₂)

⁴T_1g(F)→⁴T_2g(F) (v₃)

³A_2g(F)→³T_2g(F) (v₁)

³A_1g(F)→³T_1g(F) (v₂)

³A_2g(F)→³T_1g(P) (v₃)

²B_1g→²A_1g(v₁)

²B_1g→²E_2g(v₂)

LMCT

17,734

9455

24,291

18,226

10,453

10

11

[Ni(L²)₂(H₂O)₂]

2.80

1.78

Octahedral

[Cu(L²)₂(H₂O)₂] 24,042

15,618

12

13

[Zn(L²)₂(H₂O)₂]

24,440

–

5.00

Octahedral

[Co(L³)₂(H₂O)₂] 23,649

⁴T_1g(F)→⁴T_1g(P) (v₁)

⁴T_1g(F)→⁴A_2g(F) (v₂)

⁴T_1g(F)→⁴T_2g(F) (v₃)

³A_2g(F)→³T_2g(F) (v₁)

³A_1g(F)→³T_1g(F) (v₂)

³A_2g(F)→³T_1g(P) (v₃)

²B_1g→²A_1g(v₁)

²B_1g→²E_2g(v₂)

LMCT

17,861

9587

24,675

18,645

10,582

14

15

[Ni(L³)₂(H₂O)₂]

3.30

1.95

Octahedral

[Cu(L³)₂(H₂O)₂] 24,272

15,847

16

17

[Zn(L³)₂(H₂O)₂]

24,468

–

4.90

Octahedral

[Co(L⁴)₂(H₂O)₂] 23,527

⁴T_1g(F)→⁴T_1g(P) (v₁)

⁴T_1g(F)→⁴A_2g(F) (v₂)

⁴T_1g(F)→⁴T_2g(F) (v₃)

17,844

9575

24,437

18,429

10,664

18

[Ni(L⁴)₂(H₂O)₂]

³A_2g(F)→³T_2g(F) (v₁) 3.20

³A_1g(F)→³T_1g(F) (v₂)

Octahedral

³A_2g(F)→³T₁g(P)(v₃)

1 3

J. Devi et al.

Table 5 (continued)

Compounds Ligand/Complex Band assignment Transitions

μ_ef(BM) Geometry

19

[Cu(L⁴)₂(H₂O)₂] 24,214

²B_1g→²A_1g(v₁)

1.85

Octahedral

15,720

24,450

²B_1g→²E_2g(v₂)

LMCT

20

[Zn(L⁴)₂(H₂O)₂]

–

Octahedral

the complexation of metal ion with hydrazones and the transitions due to aromatic

carbon (π→π*) remains unaltered. The spectra of the [Co(L¹⁻⁴)₂(H₂O)₂] com-

plexes exhibit three d–d absorption transitions in the range 23,423–23,649 cm⁻¹,

4

17,734–17,861 cm⁻¹, and 9455–9587 cm⁻¹due to T_1g(F)→⁴T_1g(P),

4

⁴T_1g(F)→⁴A_2g(F) and T_1g(F)→⁴T_2g(F) transitions which suggests octahedral

geometry of cobalt(II) complexes [41].

The ESR graph is depicted in Fig. 3 at room temperature and liquid nitrogen

temperature.

The spectra of [Ni(L¹⁻⁴)₂(H₂O)₂] complexes showed three d-d absorp-

tion transitions in the range of 24,291–24,675 cm⁻¹, 18,226–18,645 cm⁻¹and

3

10,453–10,582 cm⁻¹, ascribed to the A_2g(F)→³T_1g(P), A_1g(F)→3T_1g(F)

and A_2g(F)→³T_2g(F) transitions, respectively, which results in the octahe-

3

dral geometry of nickel(II) ions [42]. The spectra of [Cu(L¹⁻⁴)₂(H₂O)₂] com-

plexes showed two absorption transitions at 24,042–24,272, 15,618–15,847 cm⁻¹

assigned to B_1g→²A_1g(ν₁) and B_1g→²E_2g(v₂) transitions [43], and spec-

tral data of [Zn(L¹⁻⁴)₂(H₂O)₂] complexes show only one band in the range of

24,440–24,468 cm⁻¹which is attributed to LMCT transitions [44], and these com-

plexes were diamagnetic in nature with complete flled d¹⁰confguration. Based

upon the above spectral analysis and analytical data, it was conf rmed that all the

complexes have octahedral arrangement around central metal ion [45].

2

Magnetic measurement of compounds

The magnetic moment data of Co(II), Ni(II) and Cu(II) complexes were found to be

in range of 4.60–5.00 BM, 2.80–3.30 BM and 1.78–1.95 BM, respectively, which

shows the paramagnetic nature of all the three types of metal complexes. The meas-

ured μ_efvalues are in the range known for six coordinated octahedral geometry [46]

and the Zn(II) complexes shows a diamagnetic behaviour.

Fluorescence spectra of compounds

The steady-state fuorescence emission spectral analysis of the hydrazones and

their corresponding metal complexes were carried out in CHCl₃with an excita-

tion wavelength of 300 nm at 298 K. On complexation, hydrazones indicate some

remarkable changes in fuorescent properties like quenching of spectra, variation in

intensity, diference of wavelength in emission bands or emergence of new bands,

etc. Hydrazone HL²(2) observes broad fuorescent emission band at 407 nm, gets

1 3

Transition metal (II) complexes of hydrazones derived from…

Fig. 3 ESR spectrum of [Cu(L³)₂(H₂O)₂](15) at a room temperature and b liquid nitrogen temperature

1 3

J. Devi et al.

Fig. 4 Fluorescence spectra of hydrazone HL²(2) and its transition metal complexes

shifted on coordination with central metal atom and is shown in Fig. 4. The Co(II),

Ni(II), Cu(II) and Zn(II) metal complexes that exhibited bands at 410, 408, 412 and

415 nm, respectively, confrm complexation. The intensifcation in fuorescent spec-

tra (hyperchromic shift) of metal complexes can be ascribed for M→L charge trans-

fer (LMCT) transitions, which showed their extra stability [47]. The order followed

for fuorescent properties of hydrazone HL²and its metal complexes follows the

trend: Zinc(II)>Copper(II)>Cobalt(II)>Nickel(II)>HL². The enhancement in fu-

orescent intensity of zinc complexes is due to their fulflled d¹⁰confguration mak-

ing them difcult to oxidize and reduce. Based on the above data, it was revealed

that the hydrazones and their transition metal complexes are good fuorescent com-

ponents and may have good photochemical applications [48].

Conductance measurements of compounds

The molar conductance of Co(II), Ni(II), Cu(II) and Zn(II) complexes of 1×10⁻³

M

solution is found to be between 11–20 Ω⁻¹cm^{2 mol−1}, which confrmed the non-elec-

trolytic nature of compounds [31].

Thermal studies

Thermal behaviour of compounds was analysed by TG/DTA/DTG analysis, and

thermal data of the compounds were recorded between temperature 25–550 °C

1 3

Transition metal (II) complexes of hydrazones derived from…

Fig. 5 Thermo gravimetric curve of [Ni (L¹)₂(H₂O)₂] (6)

under nitrogen atmosphere with heating rate of 20 °C min⁻¹. In the current study,

thermal analysis was carried out to get valuable information about the thermal sta-

bility of synthesized complexes and to decide whether water molecules are outside

or inside the coordination sphere of metal [49–51]. The various thermal decay steps

followed by the complexes with their respectiv e mass loss are presented in Fig. 5.

The TG curve of all the complexes follows the same design of three-step decompo-

sition with mass loss till the metal oxide is formed. Thermal analysis describes that

the complexes are stable below 180 °C, which indicates that there are no hydrated

water molecules of crystallization as no mass loss was noticed up to this tempera-

ture, and the frst decay step is in the range 180–250 °C revealing the existence of

bonded water molecules to central metal atom. The second decay step takes place

between the temperature 250 °C and 350 °C with a mass loss attributed to a strong

broad exothermic peak on the TG graph agree with thermal decay process of the

one hydrazone moiety. The removal of second hydrazone moiety occurs in the range

350–550 °C. The thermal decay of all the transition metal complexes ended with

emergence of metal oxide residue[52, 53].

The three-step thermal decay process can be represented as:

[M (L¹⁻⁴)₂(H₂O)₂]→[M (L¹⁻⁴)₂(H₂O)₂] (no mass loss below 180 °C).

[M (L¹⁻⁴)₂(H₂O)₂]→[M (L¹⁻⁴)₂]+2H₂O (Decomposition of two water mole-

cules, near 180–250 °C, endothermic peak).

[M (L¹⁻⁴)₂]→Intermediate [M (L¹⁻⁴)] (Decomposition of one hydrazone moiety,

near 250–350 °C, exothermic peak).

Intermediate→Loss of other hydrazone moiety+metal oxide (Loss of another

hydrazone near 350–550 °C, exothermic peak).

Above 550 °C—metal oxide as a residue.

where M=Co(II), Ni(II), Cu(II) and Zn(II).

1 3

J. Devi et al.

The TG curve of the Ni(II) complex (6) (Fig. 5) revealed three thermal decay

stages in the range 193 to 560 °C and complex is highly stable up to 203 °C, which

indicates the absence of hydrated water molecules. The frst stage indicates a mass

loss of 5.7% (calculated 5.4%) in range 203–233 °C (DTG), which is due to the

removal of two H₂O molecules with an endothermic peak at 226 °C. The second

stage takes place in the temperature range 233–350 °C with a mass loss of 42.18%

(calculated 42.02%) with the appearance of a strong broad exothermic peak exactly

at 325 °C. DTA and DTG curve reveal the thermal decay of one hydrazone moi-

ety. In the third stage, dropping of second hydrazone moiety occurs in this tempera-

ture interval 350–550 °C with a fall in mass of 42.18% (calculated 42.02%) with the

appearance of a strong broad exothermic peak exactly at 426 °C leaving nickel oxide

as residue at the end of thermal decay process [54]. The residual mass (12.3%) is

presumed to be nickel(II) oxide.

Biological studies

Antimicrobial activity

Hydrazones (HL¹⁻⁴), their chelated transition metal complexes and standard drugs

were evaluated for antimicrobial activity (in vitro) using a serial dilution method

against two gram-positive bacteria (S. aureus, B. subtilis), 2 g negative bacteria (E.

coli, P. aeruginosa) and two fungal species (C. albicans, A. niger). Ciprofoxacin

and fuconazole drugs were used as a positive control for antibacterial and antifungal

activities, whereas DMSO is used as negative control having negligible inhibitory

efect. Minimum inhibitory concentration (MIC) in μmol/mL is depicted in Table 6

and its charted form is in Fig. 6.

Conclusion drawn from the biological data is summarized below:

1. The order of antimicrobial activity for hydrazones (HL¹⁻⁴) was found as

HL³>HL¹>HL⁴>HL², which is explained on the basis of nature of compounds

[55]. The antimicrobial evaluation of hydrazones is ascribed to the existence of

the azomethine (–C=N–) group, which have fne chelating abilities, which results

in construction of hydrogen bond with the active centres of the cell constituents,

which results in hindrance of normal life process [56]. The presence of electron

releasing methyl groups in hydrazone HL³makes it highly active.

2. In antibacterial activity, complexes 15, 16, 19 having MIC values in the range

0.0091–0.0317 μmol/mL were found to be more or equally active than standard

ciprofoxacin (MIC=0.0188 μmol/mL) with tested strains of bacteria. Among

gram-positive bacteria, complexes were more active towards B. subtilis than S.

aureus and for gram-negative bacteria complexes were more active for P. aer-

uginosa as compared to E. coli, and overall results show that compounds show

more potency for gram-negative bacteria t han gram-positive bacteria due to their

distinctive structure and thin cell wall [57, 58].

1 3

Transition metal (II) complexes of hydrazones derived from…

Table 6 Results of in vitro antimicrobial screening for hydrazones (1–4), mononuclear metal complexes

(5–20), and standard drugs (21, 22). (MIC in μmol/mL)

MIC in μmol/mL

C. no. Compounds

Gram-positive bacteria Gram-negative bacteria Fungi

S. aureus B. subtilis E. coli P. aeruginosa C. albicans A. niger

1

2

3

4

5

6

7

8

HL¹

HL²

HL³

HL⁴

0.0942

0.1892

0.0850

0.1885

0.1892

0.0425

0.0942

0.0800

0.0399

0.0397

0.0794

0.0804

0.0401

0.0797

0.0795

0.0366

0.0365

0.0091

0.0158

0.0400

0.0797

0.0199

0.0397

0.0188

–

0.1885 0.1885

0.1892 0.0946

0.1700 0.0425

0.1885 0.1885

0.0400 0.0800

0.0797 0.0797

0.0397 0.0795

0.0794 0.0397

0.0804 0.0804

0.0802 0.0401

0.0797 0.0399

0.0397 0.0795

0.0732 0.0366

0.0730 0.0365

0.0182 0.0091

0.0317 0.0158

0.0800 0.0400

0.0797 0.0397

0.0199 0.0158

0.0397 0.0793

0.0188 0.0188

0.1885

0.1892

0.0850

0.1885

0.0800

0.0399

0.0199

0.0794

0.0402

0.0401

0.0199

0.0397

0.0366

0.0365

0.0091

0.0158

0.0400

0.0797

0.0199

0.0397

0.0942

0.1892

0.1700

0.1885

0.0800

0.0797

0.0397

0.0794

0.0804

0.0802

0.0399

0.0795

0.0732

0.0730

0.0091

0.0158

0.0800

0.0797

0.0199

0.0397

[Co(L¹)₂(H₂O)₂] 0.0800

[Ni(L¹)₂(H₂O)₂] 0.0797

[Cu(L¹)₂(H₂O)₂] 0.0795

[Zn(L¹)₂(H₂O)₂] 0.0397

[Co(L²)₂(H₂O)₂] 0.0804

[Ni(L²)₂(H₂O)₂] 0.0802

[Cu(L²)₂(H₂O)₂] 0.0797

[Zn(L²)₂(H₂O)₂] 0.0397

[Co(L³)₂(H₂O)₂] 0.0366

[Ni(L³)₂(H₂O)₂] 0.0730

[Cu(L³)₂(H₂O)₂] 0.0182

[Zn(L³)₂(H₂O)₂] 0.0158

[Co(L⁴)₂(H₂O)₂] 0.0800

[Ni(L⁴)₂(H₂O)₂] 0.0797

[Cu(L⁴)₂(H₂O)₂] 0.0199

[Zn(L⁴)₂(H₂O)₂] 0.0793

9

10

11

12

13

14

15

16

17

18

19

20

21

22

Ciprofoxacin

Fluconazole

0.0188

–

0.0204

0.2000

0.1800

0.1600

0.1400

0.1200

0.1000

0.0800

0.0600

0.0400

0.0200

0.0000

S. aureus

B. subtilis

E. coli

P. aeruginosa

C. albicans

A. niger

Compounds

Fig. 6 Graph showing in vitro antimicrobial activity of hydrazones (1–4) and their transition metal com-

plexes (5–20)

1 3

J. Devi et al.

3. In case of antifungal activity, complexes 7, 11, 15, 16 and 19 were found to show

equally good inhibitory efect than standard fuconazole (MIC=0.204 μmol/mL)

having MIC values in the range 0.0091–0.0399 μmol/mL.

In conclusion, compound (HL³) and its copper and zinc complexes 15 and 16 are

found to more active antimicrobial agent in the entire series of compounds tested.

The antibacterial and antifungal evaluation reveals that the transition metal com-

plexes were observed to be more active than their parent hydrazones against same

species under similar environmental conditions, and this enhancement is explained

by on the basis of overtone’s concept of chelation theory as evidenced from liter-

ature data [59, 60]. The fuctuations in the antimicrobial study rely on the difer-

ences in ribosomes in the microbial cell or the permeability of the cell wall. The

lipid membrane surrounding the cell wall favours the movement of any lipid-soluble

materials, and it is known that lipid solubility is an major factor to control the anti-

microbial activity [61], the nature of metal ion, azomethine linkage in compounds

and chelation phenomena that play an efective role in inhibitory activity [62].

Cytotoxicity

Chemotherapy is the branch of science which deals with both localized and metas-

tasized cancers. The compounds (1–20) were tested for their cytotoxic and growth

inhibitory activities (in vitro) against three human cancer cell lines (A549, Hela,

MCF7) and one normal cell line (L₆) by the MTT assay. Doxorubicin, one of the

most active anticancer agents, was taken as a reference standard. The response

parameter was determined as the IC₅₀values, which response to the concentration

needed for 50% inhibition of cell viability [63, 64]. The correlation between the sur-

viving fraction and drug concentration was plo tted to get the survival curve of all

the tested cancer cell lines. The trend followed by hydrazones against cell lines is

HL³>HL²>HL⁴>HL¹, where HL³hydrazone is most active due to electron releas-

ing methyl group attached to benzene ring. In vitro cytotoxicity of the synthesized

compounds (1–20) is tabulated in Table 7 and bar graph representation in Fig. 7a–d.

The cytotoxic activity data reveal that:

1. Anticancer activity against human alveolar adenocarcinoma epithelial cell line

(A549): Compounds 7 and 15 displayed potent activity, with an IC₅₀value of

13.28 and 12.81 μg/mL. Other compounds 14 and 16 showed good activity with

IC₅₀<15 μg/mL, and 3, 8, 9, 11, 12, 13 and 19 gave moderate anticancer activ-

ity, while other compounds in the series do not show any activity. The results are

summarized in Table 3 and are represented in Fig. 7a.

2. The obtained results for human cervical carcinoma cell line (HeLa) demonstrated

that compounds 7, 11 and 15 exhibited very potent activity, with an IC₅₀value of

10.98, 11.05 and 11.82 μg/mL. Other compounds 13, 14 and 15 showed potency

with IC₅₀≤15 μg/mL, whereas 8, 9, 10, 12, 16 and 20 showed moderate antican-

cer activity, while remaining compounds do not show signifcant activity. The

results are presented in Fig. 7b.

1 3

Article Doi

Transition metal (II) complexes of hydrazones derived from tetralone: synthesis, spectral characterization, in vitro antimicrobial and cytotoxic studies

DOI: 10.1007/s11164-021-04413-x

Source and publish data:

Authors:

Article abstract of DOI:10.1007/s11164-021-04413-x

Full text of DOI:10.1007/s11164-021-04413-x

Products guided by the article

R&D Labs maybe for 116690-92-7

Relevant to this article

Hot Product